Post-Approval Studies

Post-Approval Studies

In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).

The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.

CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.

In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.

¿ Q-Wave myocardial infarction within three (3) weeks prior to the procedure

¿ Non Q-Wave myocardial infarction within two (2) weeks prior to the procedure

¿ Requires anticoagulation medications or has other

hemorrhagic propensity

¿ Severe arrhythmia within one week prior to the procedure

The comparison group is the historic control with a non-inferiority margin.

Sample Size

Stage 1: 10 patients with no mortalities

Stage 2: 22 patients if 1 mortality in stage 1

Futility: 2 or more mortalities

Site: 5

Sample size calculation assumptions:

Patients will be enrolled at a rate of 1 patient per month,

therefore, 30-day mortality will be known for all currently enrolled patients at the time each new patient is enrolled. The probability of 30-day mortality for the PEARL 8 device, p, has an assumed Beta prior distribution

[p] ~ Beta(0.1, 0.9)

This prior distribution is based on the previous study of the PEARL

8 device and is equivalent to observing one patient¿s worth of information with a mean 30-day mortality rate of 10%.

A minimum of 10 patients will be enrolled. There will be one interim analysis and one final analysis. At each analysis, the number of observed deaths, X, among the currently enrolled patients, N, follows a binomial distribution

[X] ~ Binomial(N, p)

The resulting posterior distribution with the currently observed data (X, N) is

[p | X,N] ~ Beta (0.1X,0.9 +N-X)

The non-inferiority margin for this study is 6.6% (4.4% + 2.2%) and the success criterion at 90%. The success stopping boundaries for this study are 0 10, and 1 22. Thus, if no deaths are observed among the first 10 patients, the study will stop for success. If 1 death is observed among the first 10 patients, the

study will continue to enroll. If among the first 22 patients, only 1 death is observed (there are no additional deaths), the study will stop for success. At any time, if 2 or more deaths are observed, the study will stop for futility.

Stage 1: 10 patients with no mortalities

Stage 2: 22 patients if 1 mortality in stage

1

Futility: 2 or more mortalities

Site: 5

Sample size calculation assumptions:

Patients will be enrolled at a rate of 1 patient per month,

therefore, 30-day mortality will be known for all currently enrolled patients at the time each new patient is enrolled. The probability of 30-day mortality for the PEARL 8 device, p, has an assumed Beta prior distribution

[p] ~ Beta(0.1, 0.9)

This prior distribution is based on the previous study of the PEARL

8 device and is equivalent to observing one patient¿s worth of information with a mean 30-day mortality rate of 10%.

A minimum of 10 patients will be enrolled. There will be one interim analysis and one final analysis. At each analysis, the number of observed deaths, X, among the currently enrolled patients, N, follows a binomial distribution

[X] ~ Binomial(N, p)

The resulting posterior distribution with the currently observed data (X, N) is

[p | X,N] ~ Beta (0.1X,0.9 +N-X)

The non-inferiority margin for this study is 6.6% (4.4% + 2.2%) and the success criterion at 90%. The success stopping boundaries for this study are 0 10, and 1 22. Thus, if no deaths are observed among the first 10 patients, the study will stop for success. If 1 death is observed among the first 10 patients, the

study will continue to enroll. If among the first 22 patients, only 1 death is observed (there are no additional deaths), the study will stop for success. At any time, if 2 or more deaths are observed, the study will stop for futility.